Hydrochloric Acid → 3-Cyclopentyl-2-(4-nitro-phenyl)-propionic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a 1 L round bottom flask containing 250 mL of 9:1 THF/DMPU at −78° C. are added under nitrogen 11 mL (78.6 mmol) anhydrous DIEA followed by rapid addition of 32 mL of 2.5 M n-BuLi in hexanes. After 10 min at −78° C. a solution of 15.4 g (74 mmol) of p-nitrophenylacetic acid, ethyl ester in 100 mL of 9:1 THF/DMPU is added dropwise over 30 min. A deep purple solution results, and the reaction mixture is stirred at −78° C. for 30 min and then cyclopentyl methyl iodide (17.6 g, 78 mmol) in 50 mL of 9:1 THF/DMPU is added. The reaction is stirred while warming slowly to RT overnight. The mixture is poured into 1 L of 1 N HCl and extracted twice with MTBE. The combined MTBE extracts are washed with brine, dried over anhydrous magnesium sulfate, filtered and reduced to an orange oil. Flash chromatography over silica eluting with 4:1 hexane/MTBE affords 3-cyclopentyl-2-(4-nitro-phenyl)-propionic acid ethyl ester as an orange oil: 1H NMR (400 MHz, CDCl3) δ 1.0-1.1 (m, 2H), 1.2 (t, 3H, J=7.2), 1.4-1.8 (m, 5H), 1.8-1.9 (m, 2H), 2.1-2.25 (m, 2H), 3.74 (t, 1H, J=7.8), 4.1 (m, 2H), 7.51 (d, 2H, J=8.8), 8.19 (d, 2H, J=8.8); LC/MS 290 (M−1).

Provenance & Evidence